rs76726076

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001278116.2(L1CAM):c.3457+18C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00164 in 1,210,593 control chromosomes in the GnomAD database, including 17 homozygotes. There are 690 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0019 ( 1 hom., 108 hem., cov: 24)

Exomes 𝑓: 0.0016 ( 16 hom. 582 hem. )

Consequence

L1CAM
NM_001278116.2 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -2.32

Publications

2 publications found

Variant links:

Genes affected

L1CAM (HGNC:6470): (L1 cell adhesion molecule) The protein encoded by this gene is an axonal glycoprotein belonging to the immunoglobulin supergene family. The ectodomain, consisting of several immunoglobulin-like domains and fibronectin-like repeats (type III), is linked via a single transmembrane sequence to a conserved cytoplasmic domain. This cell adhesion molecule plays an important role in nervous system development, including neuronal migration and differentiation. Mutations in the gene cause X-linked neurological syndromes known as CRASH (corpus callosum hypoplasia, retardation, aphasia, spastic paraplegia and hydrocephalus). Alternative splicing of this gene results in multiple transcript variants, some of which include an alternate exon that is considered to be specific to neurons. [provided by RefSeq, May 2013]

L1CAM Gene-Disease associations (from GenCC):

L1 syndrome
Inheritance: XL Classification: DEFINITIVE Submitted by: ClinGen
X-linked hydrocephalus with stenosis of the aqueduct of Sylvius
Inheritance: XL Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Genomics England PanelApp, Orphanet, G2P
MASA syndrome
Inheritance: XL Classification: STRONG, SUPPORTIVE Submitted by: Genomics England PanelApp, Orphanet
X-linked complicated corpus callosum dysgenesis
Inheritance: XL Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Genomics England PanelApp, Labcorp Genetics (formerly Invitae)
X-linked complicated spastic paraplegia type 1
Inheritance: XL Classification: SUPPORTIVE Submitted by: Orphanet

L1CAM links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant X-153863865-G-A is Benign according to our data. Variant chrX-153863865-G-A is described in ClinVar as Benign. ClinVar VariationId is 458214.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.00186 (211/113145) while in subpopulation EAS AF = 0.0167 (60/3586). AF 95% confidence interval is 0.0133. There are 1 homozygotes in GnomAd4. There are 108 alleles in the male GnomAd4 subpopulation. Median coverage is 24. This position passed quality control check.

BS2

High Hemizygotes in GnomAd4 at 108 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein
L1CAM	NM_001278116.2 link	c.3457+18C>T	intron_variant	Intron 26 of 28	ENST00000370060.7	NP_001265045.1
L1CAM	NM_000425.5 link	c.3457+18C>T	intron_variant	Intron 25 of 27		NP_000416.1
L1CAM	NM_024003.3 link	c.3457+18C>T	intron_variant	Intron 25 of 26		NP_076493.1
L1CAM	NM_001143963.2 link	c.3442+18C>T	intron_variant	Intron 24 of 25		NP_001137435.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
L1CAM	ENST00000370060.7 link	c.3457+18C>T		intron_variant	Intron 26 of 28	5	NM_001278116.2	ENSP00000359077.1

Frequencies

GnomAD3 genomes

AF:

0.00187

AC:

211

AN:

113093

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000321

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000649

Gnomad ASJ

AF:

0.00113

Gnomad EAS

AF:

0.0167

Gnomad SAS

AF:

0.000357

Gnomad FIN

AF:

0.0176

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000506

Gnomad OTH

AF:

0.000656

GnomAD2 exomes

AF:

0.00315

AC:

574

AN:

182254

AF XY:

0.00304

show subpopulations

Gnomad AFR exome

AF:

0.0000764

Gnomad AMR exome

AF:

0.000146

Gnomad ASJ exome

AF:

0.00120

Gnomad EAS exome

AF:

0.0168

Gnomad FIN exome

AF:

0.0155

Gnomad NFE exome

AF:

0.000788

Gnomad OTH exome

AF:

0.00311

GnomAD4 exome

AF:

0.00161

AC:

1772

AN:

1097448

Hom.:

Cov.:

AF XY:

0.00160

AC XY:

582

AN XY:

362862

show subpopulations

African (AFR)

AF:

0.0000758

AC:

AN:

26382

American (AMR)

AF:

0.000170

AC:

AN:

35193

Ashkenazi Jewish (ASJ)

AF:

0.00119

AC:

AN:

19378

East Asian (EAS)

AF:

0.0263

AC:

795

AN:

30197

South Asian (SAS)

AF:

0.000388

AC:

AN:

54100

European-Finnish (FIN)

AF:

0.0160

AC:

648

AN:

40486

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4133

European-Non Finnish (NFE)

AF:

0.000208

AC:

175

AN:

841519

Other (OTH)

AF:

0.00221

AC:

102

AN:

46060

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

145

217

290

362

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00186

AC:

211

AN:

113145

Hom.:

Cov.:

AF XY:

0.00306

AC XY:

108

AN XY:

35285

show subpopulations

African (AFR)

AF:

0.0000320

AC:

AN:

31211

American (AMR)

AF:

0.000648

AC:

AN:

10805

Ashkenazi Jewish (ASJ)

AF:

0.00113

AC:

AN:

2658

East Asian (EAS)

AF:

0.0167

AC:

AN:

3586

South Asian (SAS)

AF:

0.000358

AC:

AN:

2791

European-Finnish (FIN)

AF:

0.0176

AC:

111

AN:

6321

Middle Eastern (MID)

AF:

0.00

AC:

AN:

218

European-Non Finnish (NFE)

AF:

0.000506

AC:

AN:

53324

Other (OTH)

AF:

0.000648

AC:

AN:

1543

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00113

Hom.:

Bravo

AF:

0.000752

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Spastic paraplegia

Benign:1

Jan 08, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.47

(source)

DANN

Benign

0.83

PhyloP100

-2.3

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over